1. Field of the Invention
The present invention relates to a method of treating inflammatory diseases, and more particularly, to a method of treating inflammatory diseases wherein the peripheral blood of a patient suffering from an inflammatory disease is treated to remove granulocytes therefrom and then the thus-treated blood is returned to the patient for alleviating or curing the symptoms of various inflammatory diseases.
2. Description of Related Art
Phagocytes such as neutrophilic leukocytes gather in inflamed tissues, and form a cell mass having various functions such as phagocytosis, production of activated oxygen, release of granular enzymes, migration into tissues, adhesion to tissues, etc. They play a very important role in the defense mechanism of a living body against invading microorganisms.
It is known that when such a cell mass locally infiltrates excessively or chronically, significant disorders are caused in the tissue. For example, it has been reported that phagocytes, in particular neutrophilic leukocytes, play an important role in the onset mechanism of reflow disorders after ischemia of myocardial infarct, etc. (J. L. Romson, et al., Circulation, 67, 1016-1023, 1983), pulmonary edema induced by sepsis, etc., called ARDS (adult respiratory distress syndrome) (J. E. Powe, et al., Crit. care. Med., 10 712-718, 1982), multiple organ failure (E. A. Deitch, Ann. Surg., 216, 117-134, 1992), rheumatoid arthritis having a background of biological reaction and immunologic reaction (P. R. Elford, P. H. Coper, Arthritis Rheum. 34, 325-332, 1991; D. Schrier et al., Am. J. Pathol., 117, 26-29, 1984) and glumerulonephritis (L. Baud et al., Kidney Int., 20, 332-339, 1981).
In addition, although the onset of ARDS, a clinical syndrome of pulmonary edema caused as a result of tissue disorders of the lung, has many causes such as respiratory infections, physicochemical injuries given to the lung, sepsis, poisoning by drugs, and serious traumas, the histological findings of ARDS are common. That is, general pulmonary alveolus disorders, angiectasia, disorders in epithelial cells and the resultant edema formation, and accumulation of neutrophilic leukocytes are commonly found. Therefore, it is considered that neutrophilic leukocytes profoundly participate in the inflammatory reaction in ARDS (A. A. Fowler, et al., Am. Rev. Respir., 136, 1225-1231, 1987). In fact, functions of neutrophilic leukocytes in peripheral blood of a patient suffering from sepsis (S. D. Tennenburg, et al., Arch. Surg., 123, 171-175, 1988) and those in pulmonary exudates of ARDS have been found altered (T. R. Martin, et al., Am. Rev. Respir. Dis., 144, 252-262, 1991). Also, it is reported that a migration stimulation factor IL-8 (C. E. Hack, et al., Infect. Immun., 60, 2842-2852, 1992), a factor TNF which participates the activation of IL-8, (T. M. Hyers., et al., Am. Rev. Respir. Dis., 144, 268-271, 1991), and endotoxin (P. E. Parsons, et al., Am. Rev. Respir. Dis., 140, 294-301, 1989) all elevate in the patient's blood.
Accordingly, in order to treat these diseases by controlling the actions and functions of neutrophilic leukocytes, various approaches have been taken, which include: administration of N-acetylcysteine (NAC), which is an SOD against the production of activated oxygen (G. R. Bernard, et al., J. Clin. Invest., 73, 1772-1784, 1984); administration of a granulocyte elastase inhibitor (M. Ogawa, et al., Res. Comm. Chem. Path. Pharm., 55, 271-274, 1987); administration of an anti-endotoxin antibody (A. P. Wheeler, et al., Am. Rev. Respir. Dis., 142, 775-781, 1990); and application of an anti-adhesion molecular monoclonal antibody such as CD18 in an attempt to inhibit adhesion of neutrophilic leukocytes to the tissue (N. B. Vedder, et al., J. Clin. Invest., 81, 939-944, 1988).
However, any of these approaches for the treatment of inflammatory diseases cannot avoid causing adverse side effects because the substance administered to the patient is foreign to his or her body.
In view of the foregoing, the present invention is to provide a method of treating inflammatory diseases by not administering any drugs but by controlling the content of an in vivo component which participates in the onset of inflammatory diseases.
The present inventors have conducted careful studies mainly focusing on the relation between inflammatory diseases and the quantity of the inflammation-associated cells such as granulocytes and monocytes, and the relation between the concentration of these cells in blood in inflammatory diseases and the concentration of inflamed tissue, and as a result, they have found that when inflammation-associated cells are selectively removed from the peripheral blood of a patient suffering from an inflammatory disease and then the thus-treated blood is returned to the patient, the inflammatory disease is alleviated and healing of the disease is accelerated. The present invention was accomplished based on this finding.